7 May 2015Cancer Research

Outwitting the Immune System

An American biotech firm is developing a new antibody to combat cancer that also improves the patient’s feeling of well-being. Its work is based on research done by Zurich dermatologist Thomas Kündig.

Physicians at the Anderson Cancer Center in Houston, Texas, could
hardly believe their eyes and ears: A week previously they had injected cancer
patient John Baker* with cancer drug Xilonix. Until that point Baker had been
seriously ill, emaciated, and confined to bed. Now he turned up claiming to be
cured.

The doctors had their doubts, and duly examined him. They found that
the tumor was still there. Even so, Baker felt much better. This is no isolated
phenomenon: Seriously ill people treated with Xilonix have been able to leave
their beds, start eating again, and go to work. And they’re living much longer
than expected.

“Doctors weren’t able to explain it,” says Thomas Kündig, a
dermatologist at University Hospital Zurich who teaches at UZH, “until someone
realized that rather than targeting the tumor, the drug was primarily treating
the cachexia, the wasting of the body that accompanies cancer.”

Cancer leads to general illness, loss of appetite, and depression. “Generally
patients die from the cachexia rather than from the tumor itself,” explains
Kündig. “Apple founder Steve Jobs is a good example.”

Around ten percent more muscle mass

Patients treated with Xilonix not only feel better, but their bodies
also get stronger again. “Within eight weeks their muscle mass had increased
around ten percent,” says Kündig. “Given that cancer patients normally suffer a
steady loss of muscle mass, this is something we’ve never seen before.” Thomas
Kündig is following the clinical studies in Texas closely, as Xilonix is based
among other things on his research.

Kündig’s work involved investigating what happens when the secretion
of interleukin 1alpha is inhibited. Interleukin 1alpha is a messenger that is
secreted when there is an immune response in the body, for example when the
immune system is mobilized against cancer cells. While this immune response is
vitally important for us because it protects the body from infection by
attacking viruses, bacteria, and other foreign bodies, it can also have a
downside.

Cancer enslaves the immune system

In the case of cancer this even happens frequently. Tumors lead to
inflammation. “For a long time the strong inflammatory reactions induced by tumors
were viewed as something positive,” explains Thomas Kündig. “They were thought
to be a sign that the immune system was fighting the cancer.” But now it’s
becoming increasingly clear that this inflammation is more of a help than a
hindrance to the tumor, because the inflammation leads to the creation of new
blood vessels that supply the tumor with the large amounts of energy it needs.
The inflammation also destroys surrounding tissue and bone, enabling the cancer
to grow and spread.

In other words, the immune response triggered by interleukin 1alpha
harms the body and helps the cancer. “Cancer enslaves the immune system and
uses it for its own purposes,” says Kündig. “If we can prevent this immune
response, it could inhibit the development of the tumor.” Interleukin 1alpha is
one of the keys to this immune response, because secretion of the messenger
triggers a cascade of immune reactions.

So Kündig’s aim was to neutralize interleukin 1alpha. He was helped by
the fact that a Danish research group had found an anti-interleukin antibody in
healthy humans and had been able to clone it.

Antibody against interleukin 1alpha

Now an American biotech firm, XBiotech, has advanced an
anti-interleukin-1alpha antibody to the clinical development stage. The drug is
called Xilonix. After successful preliminary studies on mice and rats, Xilonix
was used on an initial group of cancer patients, including John Baker, in
Houston. A total of 30 patients were treated.

As related above, the trials were astonishingly successful. Officials
at the FDA, the US drug licensing authority, were so impressed by the initial
results that they approved fast track designation for clinical trials of
Xilonix. This means that fewer patients have to be included in the trials, and
review processes are considerably shorter. “The FDA has recognized that this
drug is a new way of helping seriously ill people,” says Kündig. “At the moment
nothing else like it exists.”

Fighting cancer and boosting patient well-being

This is particularly true given the way that unlike conventional
chemotherapy, which often leads to a massive deterioration in quality of life,
Xilonix boosts patients’ well-being in addition to tackling the tumor itself.

Considering the serious side-effects, many patients with cancer at an
advanced state elect not to have therapy or to discontinue it. This means
Xilonix has the potential to revolutionize the treatment of cancer: Instead of
having to choose between therapy and quality of life, patients could opt for
therapy that actually improves their quality of life.

*Name changed

Thomas Gull is editor at UZH Magazin.

1 Reader Comment

Shiyong Li commented on
23 May 2015, 19:01How is the mechanism
This is great work, a new sight in cancer immunotherapy. As essay said "Generally patients die from the cachexia rather than from the tumor itself". IL-1 has a bad role in tumor development, specially contributes in cachexia formation. Neutralizing of IL-1 by antibody is a good way to impair this progress and has a good clinic result. But I think this is not enough, it can be united with other anti-tumor treatment such as IL-2 and tumor specific antibody. This is why I care about the mechanism that anti-IL-1 can have effect on curing human cancer, the essay shows that the tumor of patient was still there. I was thinking is there a checkpoint that an inflammation can change the effect from anti-tumor cell to protect tumor cell? I used to make sure thatdrug induced inflammation truly can prevent tumor growth. How to make immune system not to be slaved by tumor is a crucial step for tumor inmmunotherapy. Maybe this work is a good start.

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